PEX3

peroxisomal biogenesis factor 3, the group of Peroxins

Basic information

Region (hg38): 6:143450805-143490616

Links

ENSG00000034693

∙ NCBI:8504 ∙ OMIM:603164 ∙ HGNC:8858 ∙ Uniprot:P56589 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

peroxisome biogenesis disorder 10A (Zellweger) (Moderate), mode of inheritance: AR
peroxisome biogenesis disorder 10A (Zellweger) (Definitive), mode of inheritance: AR
Zellweger spectrum disorders (Supportive), mode of inheritance: AR
peroxisome biogenesis disorder 10A (Zellweger) (Strong), mode of inheritance: AR
peroxisome biogenesis disorder (Definitive), mode of inheritance: AR
peroxisome biogenesis disorder 10B (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Peroxisome biogenesis factor disorder 3; Peroxisome biogenesis disorder 10A (Zellweger); Peroxisome biogenesis disorder 10B	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal	10968777; 10679269; 10942428; 27557811

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PEX3 gene.

not_provided (325 variants)
Peroxisome_biogenesis_disorder_10A_(Zellweger) (27 variants)
Inborn_genetic_diseases (22 variants)
PEX3-related_disorder (15 variants)
not_specified (7 variants)
Peroxisome_biogenesis_disorder_10B (5 variants)
Peroxisome_biogenesis_disorder (3 variants)
Peroxisome_biogenesis_disorder_1A_(Zellweger) (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PEX3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003630.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	71 clinvar	2 clinvar	76
missense		5 clinvar	124 clinvar	4 clinvar		133
nonsense	8 clinvar	3 clinvar	1 clinvar			12
start loss		1				1
frameshift	8 clinvar	1 clinvar	1 clinvar			10
splice donor/acceptor (+/-2bp)	1 clinvar	7 clinvar	1 clinvar			9
Total	17	17	130	75	2

Highest pathogenic variant AF is 0.000017793545

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PEX3	protein_coding	protein_coding	ENST00000367591	12	39204

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0163	0.983	125722	0	26	125748	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.19	145	191	0.759	0.00000890	2439
Missense in Polyphen		37	64.308	0.57536		846
Synonymous	0.703	60	67.3	0.891	0.00000317	695
Loss of Function	3.26	8	25.9	0.309	0.00000153	276

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000265	0.000265
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000971	0.0000967
Middle Eastern	0.0000544	0.0000544
South Asian	0.000163	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Involved in peroxisome biosynthesis and integrity. Assembles membrane vesicles before the matrix proteins are translocated. As a docking factor for PEX19, is necessary for the import of peroxisomal membrane proteins in the peroxisomes. {ECO:0000269|PubMed:10848631, ECO:0000269|PubMed:15007061}.;
Disease: DISEASE: Peroxisome biogenesis disorder 10A (PBD10A) [MIM:614882]: A fatal peroxisome biogenesis disorder belonging to the Zellweger disease spectrum and clinically characterized by severe neurologic dysfunction with profound psychomotor retardation, severe hypotonia and neonatal seizures, craniofacial abnormalities, liver dysfunction, and biochemically by the absence of peroxisomes. Additional features include cardiovascular and skeletal defects, renal cysts, ocular abnormalities, and hearing impairment. Most severely affected individuals with the classic form of the disease (classic Zellweger syndrome) die within the first year of life. {ECO:0000269|PubMed:10848631, ECO:0000269|PubMed:10958759}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Peroxisome biogenesis disorder 10B (PBD10B) [MIM:617370]: A moderately severe peroxisome biogenesis disorder belonging to the Zellweger disease spectrum. PBD10B is characterized by neonatal jaundice, dysmorphic features, delayed psychomotor development, axial hypotonia that can progress to severe spastic paraparesis with hyperreflexia, nephrocalcinosis, neurogenic bladder, nystagmus, and cataracts. Laboratory studies show increased levels of very long-chain fatty acids. Inheritance is autosomal recessive. {ECO:0000269|PubMed:27557811}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Peroxisome - Homo sapiens (human);ABC transporters in lipid homeostasis;Transport of small molecules;ABC-family proteins mediated transport (Consensus)

Recessive Scores

pRec: 0.249

Intolerance Scores

loftool: 0.593
rvis_EVS: -0.07
rvis_percentile_EVS: 48.12

Haploinsufficiency Scores

pHI: 0.331
hipred: Y
hipred_score: 0.622
ghis: 0.626

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: S
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.731

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Pex3
Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype; limbs/digits/tail phenotype; hematopoietic system phenotype; skeleton phenotype; vision/eye phenotype;

Gene ontology

Biological process: peroxisome organization;peroxisome membrane biogenesis;protein import into peroxisome membrane;transmembrane transport
Cellular component: nucleoplasm;peroxisome;peroxisomal membrane;integral component of peroxisomal membrane;endoplasmic reticulum;cytosol;membrane;protein-containing complex;protein-lipid complex
Molecular function: protein binding;lipid binding;protein binding, bridging;protein dimerization activity